Pathways

Mexiletine is an oral drug used as a Type 1B antiarrhythmic drug. It is used to treat conditions including sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. Mexiletine acts in neurons where it inhibits voltage gated sodium channels in the pre synaptic neurons. In neurons, voltage gated sodium channels allow sodium to come into the neuron triggering the depolarization phase. the potassium channels are responsible for the repolarization phase to bring the neuron back to resting potential. The action potentials created travel down the axon of the neuron and at the nerve terminal, calcium channels open, allowing calcium to enter the cell. Calcium entry causes synaptic vesicles containing neurotransmitters like glutamate to fuse with the membrane and expel the neurotransmitter into the synapse. Glutamate binds to AMPA and NMDA receptor on the post synaptic neurons where they cause excitation of the neuron. By blocking the voltage gated sodium channels, mexiletine prevents the depolarization phase, inhibiting action potential generation and the release of excitatory neurotransmitter like glutamate. Pre and post synaptic neuronal firing are therefore reduced. Mexiletine works as a “use-dependent” block. This means that it preferentially binds to channels that are being opened. In neurons that are repetitively firing, their sodium channels are being opened more often, and as a result, mexiletine is able to produce a greater block in these neurons. It also possesses some anticholinergic and local anesthetic properties. Side effects of mexiletine include nausea, vomiting, headaches, feeling dizzy, or feeling hot and flushed.

Mezlocillin is a broad-spectrum penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Mezlocillin binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts the final stage of bacterial cell wall synthesis and results in the weakening of the bacterial cell wall and eventually causing cell lysis.

mglur5--> erk

Mianserin is an H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Mianserin also inhibits the H1 histamine receptor on bronchiole smooth muscle myocytes. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin.Calcium bound calmodulin is required for the activation of myosin light chain kinase. This prevents the phosphorylation of myosin light chain 3, causing an accumulation of myosin light chain 3. This causes muscle relaxation, opening up the bronchioles in the lungs, making breathing easier.

Mianserin is an H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Mianserin inhibits the H1 histamine receptor on blood vessel endothelial cells. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin. Calcium bound calmodulin is required for the activation of the calmodulin-binding domain of nitric oxide synthase. The inhibition of nitric oxide synthesis prevents the activation of myosin light chain phosphatase. This causes an accumulation of myosin light chain-phosphate which causes the muscle to contract and the blood vessel to constrict, decreasing the swelling and fluid leakage from the blood vessels caused by allergens.

Mianserin is an H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Metabolites of Mianserin are predicted with biotransformer.

Micafungin, also known as Mycamine, is an echinocandin antifungal agent used for the treatment of candidemia, acute disseminated candidiasis, and certain other fungal infections..More commonly, Micafungin is used against Aspergillus infections, and only used against some Candida infections. It is also used to treat the prophylaxis of Candida infections during stem cell transplantation. It is a glucan synthesis inhibitor which is essential for cell wall synthesis. Micafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This prevents the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, which ultimately leads to osmotic instability and cell death.